Structure-Based Approach toward Identification of Inhibitory Fragments for Eleven-Nineteen-Leukemia Protein (ENL)

David Heidenreich; Moses Moustakim; Jurema Schmidt; Daniel Merk; Paul E. Brennan; Oleg Fedorov; Apirat Chaikuad; Stefan Knapp

doi:10.1021/acs.jmedchem.8b01457

Structure-Based Approach toward Identification of Inhibitory Fragments for Eleven-Nineteen-Leukemia Protein (ENL)

David Heidenreich, Moses Moustakim, Jurema Schmidt, Daniel Merk, Paul E. Brennan, Oleg Fedorov, Apirat Chaikuad, Stefan Knapp

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Lysine acetylation is an epigenetic mark that is principally recognized by bromodomains, and recently structurally diverse YEATS domains also emerged as readers of lysine acetyl/acylations. Here we present a crystallography-based strategy and the discovery of fragments binding to the ENL YEATS domain, a potential drug target. Crystal structures combined with synthetic efforts led to the identification of a submicromolar binder, providing first starting points for the development of chemical probes for this reader domain family.

Original language	English
Pages (from-to)	10929-10934
Number of pages	6
Journal	Journal of Medicinal Chemistry
Volume	61
Issue number	23
DOIs	https://doi.org/10.1021/acs.jmedchem.8b01457
State	Published - 13 Dec 2018
Externally published	Yes

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title = "Structure-Based Approach toward Identification of Inhibitory Fragments for Eleven-Nineteen-Leukemia Protein (ENL)",

abstract = "Lysine acetylation is an epigenetic mark that is principally recognized by bromodomains, and recently structurally diverse YEATS domains also emerged as readers of lysine acetyl/acylations. Here we present a crystallography-based strategy and the discovery of fragments binding to the ENL YEATS domain, a potential drug target. Crystal structures combined with synthetic efforts led to the identification of a submicromolar binder, providing first starting points for the development of chemical probes for this reader domain family.",

author = "David Heidenreich and Moses Moustakim and Jurema Schmidt and Daniel Merk and Brennan, \{Paul E.\} and Oleg Fedorov and Apirat Chaikuad and Stefan Knapp",

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doi = "10.1021/acs.jmedchem.8b01457",

language = "English",

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T1 - Structure-Based Approach toward Identification of Inhibitory Fragments for Eleven-Nineteen-Leukemia Protein (ENL)

AU - Heidenreich, David

AU - Moustakim, Moses

AU - Schmidt, Jurema

AU - Merk, Daniel

AU - Brennan, Paul E.

AU - Fedorov, Oleg

AU - Chaikuad, Apirat

AU - Knapp, Stefan

PY - 2018/12/13

Y1 - 2018/12/13

N2 - Lysine acetylation is an epigenetic mark that is principally recognized by bromodomains, and recently structurally diverse YEATS domains also emerged as readers of lysine acetyl/acylations. Here we present a crystallography-based strategy and the discovery of fragments binding to the ENL YEATS domain, a potential drug target. Crystal structures combined with synthetic efforts led to the identification of a submicromolar binder, providing first starting points for the development of chemical probes for this reader domain family.

AB - Lysine acetylation is an epigenetic mark that is principally recognized by bromodomains, and recently structurally diverse YEATS domains also emerged as readers of lysine acetyl/acylations. Here we present a crystallography-based strategy and the discovery of fragments binding to the ENL YEATS domain, a potential drug target. Crystal structures combined with synthetic efforts led to the identification of a submicromolar binder, providing first starting points for the development of chemical probes for this reader domain family.

UR - https://www.scopus.com/pages/publications/85057782410

U2 - 10.1021/acs.jmedchem.8b01457

DO - 10.1021/acs.jmedchem.8b01457

M3 - Article

C2 - 30407816

AN - SCOPUS:85057782410

SN - 0022-2623

VL - 61

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EP - 10934

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 23

ER -

Structure-Based Approach toward Identification of Inhibitory Fragments for Eleven-Nineteen-Leukemia Protein (ENL)

Abstract

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